Guilherme R. Teodoro
Kassapa Ellepola
Chaminda J. Seneviratne2*- 1Oral Biopathology Graduate Program, São José dos Campos Institute of Science and Technology, Universidade Estadual Paulista, São José dos Campos, Brazil
- 2Oral Sciences, Faculty of Dentistry, National University of Singapore, Singapore, Singapore
- 3Department of Environmental Engineering and Biopathology Graduate Program, São José dos Campos Institute of Science and Technology, Universidade Estadual Paulista, São José dos Campos, Brazil
There has been a sharp rise in the occurrence of Candida infections and associated mortality over the last few years, due to the growing body of immunocompromised population. Limited number of currently available antifungal agents, undesirable side effects and toxicity, as well as emergence of resistant strains pose a considerable clinical challenge for the treatment of candidiasis. Therefore, molecules that derived from natural sources exhibiting considerable antifungal properties are a promising source for the development of novel anti-candidal therapy. Phenolic compounds isolated from natural sources possess antifungal properties of interest. Particularly, phenolic acids have shown promising in vitro and in vivo activity against Candida species. However, studies on their mechanism of action alone or in synergism with known antifungals are still scarce. This review attempts to discuss the potential use, proposed mechanisms of action and limitations of the phenolic acids in anti-candidal therapy.
Introduction
Candida species are a major group of fungal pathogens in humans, particularly among immunocompromised and hospitalized patients (Cuellar-Cruz et al., 2012). Candida albicans inhabits various body surfaces like oral cavity, gastrointestinal tract, vagina, and skin of the healthy individuals as a commensal organism (Kleinegger et al., 1996; Huffnagle and Noverr, 2013). Host-related factors can predispose the transformation of harmless Candida into an opportunistic pathogen, causing infection or candidiasis in superficial mucous surfaces which can progress into invasive mycoses (Nett and Andes, 2006). Foregoing factors include, but not limited to immuno-suppression, prolonged treatment with wide-spectrum antibiotics and chronic diseases (Kullberg and Arendrup, 2015; Polke et al., 2015). The epidemiology of invasive candidiasis varies geographically (Morgan, 2005; Pfaller et al., 2011). It significantly increases the period of hospitalization, economic burden and mortality, especially in ICU patients or those under chemotherapy or with a history of abdominal surgery (Falagas et al., 2006; Berdal et al., 2014; Drgona et al., 2014).
Only few classes of antifungals such as polyenes, azoles, echinocandins, allylamines, and flucytosine are available for the treatment of Candida infections (Sanglard et al., 2009). However, there are various undesirable properties, most importantly the dose-related toxicity in aforementioned antifungals (Chandrasekar, 2011). Ideally, an antifungal should have null or reduced toxicity toward human cells (Wong et al., 2014). For instance, amphotericin B is a polyene available for systemic administration, but its use has been limited due to its systemic side effects such as nephrotoxicity (Odds et al., 2003). Azole antifungals have some side effects associated with gastrointestinal, hepatic, and endocrinologic disorders and interfere with oxidative drug metabolism in the liver (Joly et al., 1992).
In addition, rising drug resistance is an inevitable problem. In particular, Candida glabrata and Candida krusei show intrinsic resistance to fluconazole, the drug of choice for AIDS patients (Kanafani and Perfect, 2008; Siikala et al., 2010; Rautemaa and Ramage, 2011). Drug resistance has already been reported for recently introduced echinocandin antifungal agents (Hakki et al., 2006; Ben-Ami et al., 2011; Clancy and Nguyen, 2011; Seneviratne et al., 2011). Moreover, biofilm mode of Candida is known to be highly resistant to antifungal agents (Chandra et al., 2005; Niimi et al., 2010). Therefore, it is necessary to discover new antifungal agents or safer alternatives to improve the efficacy of treatment against Candida infections. In this regard, antifungal agents based on natural resources, such as phenolic compounds may be an alternative strategy to negate the rising antifungal drug resistance (Negri et al., 2014). This review attempts to critically analyze the possible use of phenolic acids as a therapeutic strategy against Candida infections.
Phenolic compounds are widely found in plant foods (fruits, cereal grains, legumes, and vegetables) and beverages (tea, coffee, fruits juices, and cocoa). The most common phenolic compounds are phenolic acids (cinnamic and benzoic acids), flavonoids, proanthocyanidins, coumarins, stilbenes, lignans, and lignins (Figure 1; Cowan, 1999; Chirinos et al., 2009; Khoddami et al., 2013). The anti-Candida properties of phenolic compounds that have been widely reported in the literature include inactivation of enzyme production (Evensen and Braun, 2009) and anti-biofilm effect (Evensen and Braun, 2009; Shahzad et al., 2014).
FIGURE 1. Examples of phenolic compounds and main derivates classified as phenolic acids.
Phenolic acids are derivatives of hydrocinnamic, hydrobenzoic, phenylacetic, and phenylpropionic acids (Figures 1 and 2; Pereira et al., 2009; Cueva et al., 2010). Phenolic acids commonly exist as esters, glycosides or amides in nature, but not in their free form. The determining factor for characterization of phenolic acids is the number and the location of hydroxyl groups on the aromatic ring. Some natural sources are rich in phenolic acids and shown to possess a promising action against Candida (Table 1). In this review, we discuss the anti-candidal activity of the phenolic acid compounds, possible mechanism of actions and future directions.
FIGURE 2. General chemical structures of the phenolic acids [based on Pereira et al. (2009) and Cueva et al. (2010)].
TABLE 1. Phenolic acids derived from plants extracts showing activity against Candida sp.
Antifungal Activity of Phenolic Acids Against Candida Species
Natural extracts containing phenolic acids have demonstrated antifungal activity against Candida species (Table 1). Phenolic acid derivatives isolated from these sources such as gallic, caffeic, cinnamic, benzoic, protocatechuic, and phenylacetic acids also have antifungal activity (Table 2). However, the antifungal effect of the natural extracts may vary due to the differences in the quantity and the type of phenolic acid. In addition, the solvents used for extraction may also affect the antifungal effect. Moreover, other compounds present in natural extracts may act synergistically with phenolic acids to enhance the overall antifungal effect (Pereira et al., 2007; Nowak et al., 2014). Therefore, phenolic acids derived from different natural sources have highly variable MIC values against Candida (Table 2). Hence, a clear understanding of the composition of phenolic acids present in the natural extract is important to assess its potential as an antifungal agent (Salvador et al., 2004; Rangkadilok et al., 2012).
TABLE 2. Evidences from literature regarding anti-Candida effect of phenolic acids.
The main Candida virulence factors are exoenzymes production, biofilm formation, adherence, and dimorphism (Vuong et al., 2004; Netea et al., 2008; Williams et al., 2011). Few studies have demonstrated the influence of phenolic acids against these factors. Anti-biofilm effect of phenolic acids against Candida sp. was reported (Wang et al., 2009; Alves et al., 2014; De Vita et al., 2014). However, the studies used only reference samples or did not cite the tested strain (Table 2). The anti-biofilm effect of these molecules should be carried out with clinical isolates in vitro and in vivo, since the ultimate goal of using these molecules is to treat candidiasis and a wider range of strains could provide more reliable results. Besides that, it also has found an influence of caffeic acid derivate against the Candida dimorphism (Sung and Lee, 2010).
However, several studies described effect on Candida virulence factors of some others phenolic molecules. For instance, bisbibenzyl stimulates the synthesis of farnesol, an inhibitor of hyphae formation, via upregulation of Dpp3 gene (Zhang et al., 2011). Hence, bisbibenzyl may reduce C. albicans hyphal formation and affect biofilm formation. Moreover, anti-hyphae effect in C. albicans was also found following the treatment with epigallocatechin-gallate (Han, 2007), licochalcone A, gladribin (Messier and Grenier, 2011), and thymol (Braga et al., 2007). Additionally, eugenol reduces germ tube formation in C. albicans (Pinto et al., 2009). Beyond that, several studies have shown anti-biofilm (Messier et al., 2011; Alves et al., 2014; Rane et al., 2014; Shahzad et al., 2014) and anti-adhesive (Feldman et al., 2012; Rane et al., 2014; Shahzad et al., 2014) activities of phenolics against Candida.
The number of studies on other phenolic molecules on Candida virulence factors with interesting results inspires a carefully investigation of phenolic acids influence on these factors.
Mechanism of Action, Biological Pathways, and Synergism with Antifungal Agents of Phenolic Acids Against Candida
In order to obtain some insights on the antifungal activity of phenolic acids, herein we compare the existing data along the lines of mechanism of action, synergy with known antifungal agents and others biological pathways (Figure 3).
FIGURE 3. Described mechanisms of action and biological pathways of some phenolic acids against Candida. (1) Ma et al. (2010); (2) Cheah et al. (2014); (3,4) Sung and Lee (2010); (5) Conti et al. (2013); (6) Alves et al. (2014); (7) De Vita et al. (2014); (8) Wang et al. (2009).
Mechanisms of Action and Biological Pathways
Phenolic acids such as ferulic and gallic acids are known to affect the cell membrane of Gram-positive and Gram-negative bacteria leading to a change in cell surface hydrophobicity and charge, ultimately causing leakage of cytoplasmic content (Borges et al., 2013). A similar effect has been suggested for the caffeic acid derivative on Candida cytoplasmatic membrane (Sung and Lee, 2010). Furthermore, a possible effect on the C. albicans cell wall has been shown for caffeic acid derivatives which may interfere with 1,3-β-glucan synthase (Ma et al., 2010).
It is noteworthy that polyene antifungals also cause pouring of cellular contents through direct binding to ergosterol, distorting the membrane function. Also, azole antifungal agents inhibit biosynthesis of ergosterol (Vanden Bossche et al., 2004). No study on the effect of phenolic acid on the ergosterol composition or biosynthesis could be detected.
Mode of action of several others phenolic compounds provide some clues to deduce the mechanism of phenolic acids. For instance, isoquercetin (Yun et al., 2015), curcumin (Lee and Lee, 2014), and lariciresinol (Pinto et al., 2009) can damage the C. albicans cell membrane. On the other hand, eugenol and methyleugenol cause considerable reduction in the ergosterol biosynthesis in Candida and subsequently affecting the cell membrane (Ahmad et al., 2010b). Similar effect has been observed with epigallocatechin-3-gallate (Navarro-Martinez et al., 2006), thymol and carvacrol (Ahmad et al., 2011). Besides, cardanol demonstrated chitin-binding ability in C. albicans cell wall (Mahata et al., 2014).
Few studies have found about others biological pathways of phenolic acids against Candida. Exemplifying, an in vitro immunoregulatory effect on monocytes against C. albicans by cinnamic acid (Conti et al., 2013) and a inhibition of C. albicans isocitrate lyase enzyme activity after treatment with caffeic acid (Cheah et al., 2014) was reported. However, several studies have suggested that the other biological pathways and cellular targets of others phenolic compounds may be different from that of existing antifungal agents. Some phenolic compounds have shown to induce apoptotic mechanisms in Candida, thereby contributing to their antifungal activity (Zore et al., 2011). For instance, eugenol inhibits the cell cycle at G1, S, and G2-M phases in C. albicans and consequently induces apoptosis. Another phenolic compound, curcumin also induces apoptosis in C. albicans, by increasing the reactive oxygen species (ROS) and induction of CaMCA1 gene expression (Cao et al., 2009). On the contrary, baicalein increases ROS causing perturbation in mitochondrial homeostasis in C. krusei without inducing apoptosis (Kang et al., 2010). Methyl chavicol seemed to induce aptotosis in C. albicans although the exact pathway is still not clear (Khan et al., 2014). Blocking effect of thymol, carvacrol (Ahmad et al., 2013) and baicalein (Huang et al., 2008) on the drug transporter pumps in Candida has been demonstrated using rhodamine 6G dye. Inhibition of efflux transporters results in accumulation of antifungal compounds inside the cell making Candida highly susceptible to the antifungal agent (Huang et al., 2008). These helpful anti-Candida biological pathways observed for phenolic molecules, mainly on the drug transporters pumps may contribute to elucidate the possible effects of phenolic acids against Candida.
Another aspect to be considered is that previous studies reported that some Candida species were able to metabolize phenolic acids (Middelhoven et al., 1992; Middelhoven, 1993). C. parapsilosis was able to grow in the presence of some phenolic acids after 3 days of cultivation. On the other hand, C. tropicalis was unable to grow in the presence of phenolic acids even after 14 days of cultivation (Middelhoven, 1993). These evidences should be better investigated in the future. Further studies are warranted to obtain a deeper understanding of the mechanism of action and others biological pathways of phenolic acids on Candida cells.
Synergism with Existing Antifungal Agents
Apart from rising antifungal resistance, there are other important limitations in the existing antifungal agents, such as inadequate spectrum of activity, poor bioavailability, small tolerance index, interactions with other drugs, inadequate pharmacokinetic profile, and considerable toxic effects (Lewis and Graybill, 2008; Pfaller et al., 2010). Although phytochemicals remain an important source for the discovery of new antifungal agents, micro-plate based in vitro screening assays have not shown higher effectiveness of plant extracts when compared to the existing antifungal agents with higher efficacy (Newman and Cragg, 2012). Hence, in general, plant extracts with higher minimum inhibitory concentrations (MICs) such as 1000 μg/ml are considered ineffective (Morales et al., 2008).
Therefore, some studies have explored the possibility of synergistic activity of phenolic acids and existing antifungal agents in order to maximize the antifungal effect. It is a good strategy to study the synergistic effect when MIC values of phenolic acids against Candida are highly variable (Rauha et al., 2000; Kalinowska et al., 2014). Synergistic effect of benzoic acid with amphotericin B and itraconazole against C. albicans has been reported in literature (Faria et al., 2011; Table 3). However, mechanism of this synergistic effect of phenolic acids and conventional antifungal agents is poorly understood. Therefore, it is important to examine similar synergistic effects shown by others phenolic compounds and conventional antifungal agents in order to obtain some insight.
TABLE 3. Synergism of phenolic compounds with traditional antifungals in their action against Candida albicans.
A promising synergism between phenolic compounds and fluconazole against resistant strains of Candida tropicalis was described recently (da Silva et al., 2014). Several other studies have also demonstrated a significant synergism between other known antifungals and phenolic compounds against C. albicans (Table 3). Some studies suggested that the synergism is due to the induction of apoptosis by an increase in the production of ROS. Hence, it was found that amphotericin B together with baicalein or curcumin increases the production of ROS (Sharma et al., 2010; Fu et al., 2011). A similar effect has been observed with fluconazole and curcumin (Sharma et al., 2010).
Another hypothesis for the aforementioned synergism is the association between folic acid cycle and ergosterol biosynthesis pathways of C. albicans. Hence, epigallocatechin-gallate, a phenolic compound was demonstrated to have a synergistic antifungal effect on Candida when combined with itraconazole or ketoconazole (Navarro-Martinez et al., 2006). Azoles directly inhibit the ergosterol biosynthesis while epigallocatechin-gallate has an antifolatic effect that indirectly affects the ergosterol biosynthesis. Epigallocatechin-gallate causes a depletion of the enzyme S-adenosylmethionine which in turn affects the enzyme Sterol C24 methyltransferase. Hence, lower production of C24 methyltransferase negatively affects the ergosterol biosynthesis. Direct and indirect effects on ergosterol biosynthesis explain the synergism between epigallocatechin-gallate and azoles (Navarro-Martinez et al., 2006).
Another study has shown that phenolic compounds such as thymol and carvacrol significantly decrease the expression levels of virulence genes CDR1 and MDR1 in fluconazole-resistant C. albicans (Ahmad et al., 2013). An in vivo study on systemic candidiasis in mice demonstrated that following the treatment with honokiol and fluconazole, the survival rate was 100% while a monotherapy showed only a survival rate of 80% to fluconazole and 20% to honokiol, respectively. Furthermore, the synergism of these two compounds led to a notable reduction in C. albicans counts in mouse kidneys compared with the fluconazole treatment alone (Jin et al., 2010). Similarly, mice treated with epigallocatechin-gallate and amphotericin B survived approximately 24 and 30 days longer when compared to the groups treated only with epigallocatechin-gallate or amphotericin B, respectively (Han, 2007). Considering the foregoing evidence obtained for other phenolic compounds, it is likely that potential of synergism exists between known antifungal agents and phenolic acids and this possibility needs to be examined in future.
Safety of the Phenolic Acids In vitro and In vivo
An ‘ideal’ antifungal agent for Candida infections should not have side effects or toxicity (Chapman et al., 2008; Wong et al., 2014). However, in reality, all the antifungals currently in use have some side effects on gastrointestinal tract, liver and kidney (Wingard et al., 1999; Bates et al., 2001). Therefore, practically one would expect to have some dose-related side effects from any new antifungal agent. It is imperative to understand this limitation in order to appreciate promising qualities of the drug under investigation. DNA-damaging effect of phenolic acids has been observed in p53R cell lines treated with gallic acid (Hossain et al., 2014). Moreover, in vivo hepatotoxicity was observed in rats when given a diet supplemented with more than 200 mg/kg/day of gallic acid (Galati et al., 2006). In addition, hematological disorders, as well as liver and kidney weight increase were observed in rats fed with 0.6–5% of gallic acid daily for 13 weeks (Niho et al., 2001).
A potential carcinogenicity was observed on the fore-stomach of rats when fed with a powdered diet containing 0.4% of caffeic acid for up to 28 weeks (Hirose et al., 1998). The clastogenic power of caffeic and cinnamic acids have been described in vitro (Maistro et al., 2011). Subcronic administration of protocatechuic acid (0.1% in drinking water) for 60 days has shown a possible liver and kidney toxicity in mice (Nakamura et al., 2001). Sodium benzoate and sodium phenylacetate have been used in the treatment of acute hyperammonaemia and are derived from benzoic acid and phenylacetic acid respectively. Inappropriate doses of both substances may cause plasma acidosis, hypotension, cerebral edema and other neurotoxical effects, sometimes even death of patients (Kaufman, 1989; Praphanphoj et al., 2000). Phenylacetic acid can also affect the osteoblastic functions in vitro and increase cell proliferation in the alveolar region (Kaufmann et al., 2005; Yano et al., 2007). Sodium and potassium benzoates could be clastogenic, mutagenic and cytotoxic to human lymphocytes in vitro (Zengin et al., 2011). Therefore, is imperative to examine the dose-related toxicity of phenolic acids in a series of comprehensive in vitro, in vivo and clinical studies before administration as an antifungal agent.
Conclusion
Phenolic acids demonstrate considerable antifungal properties against Candida. Previous studies have shown phenolic acid compounds possess considerable anti-adhesion, anti-biofilm effects, and inhibitory activity on morphogenesis and exoenzyme production of Candida species. However, hitherto no clear mechanism of action of phenolic acids on Candida cells and virulence factors has been described compared to the existing antifungal agents. Interestingly, there is substantial evidence of the synergistic effect of phenolic acids and existing antifungal agents which may become a promising anti-candidal strategy. However, more studies are in demand for a conclusive statement regarding their role. Therefore, we propose that more comprehensive studies are mandatory to obtain evidence regarding the suitability of the use of phenolic acids as a successful antifungal agent in future.
Author Contributions
GT conceived, designed, did the literature review, provided and wrote the manuscript. KE assisted in the preparation, design, final review, and co-wrote the manuscript. CK-I and CS conceived, designed, assisted in the literature and final review, and co-wrote the manuscript.
Conflict of Interest Statement
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Acknowledgments
The authors are grateful to Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, #/2013/0037-1 and #2012/16805-5) for financial support and fellowship to GT, to Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) for sandwich Ph.D. fellowship to GT, and to National University of Singapore for providing Ph.D. fellowship to KE. GT’s Ph.D. internship at NUS was supported by NUS-Start-up grant (R-221-000-064-133) to CS.
References
Ahmad, A., Khan, A., Akhtar, F., Yousuf, S., Xess, I., Khan, L. A., et al. (2011). Fungicidal activity of thymol and carvacrol by disrupting ergosterol biosynthesis and membrane integrity against Candida. Eur. J. Clin. Microbiol. Infect. Dis. 30, 41–50. doi: 10.1007/s10096-010-1050-8
Ahmad, A., Khan, A., Khan, L. A., and Manzoor, N. (2010a). In vitro synergy of eugenol and methyleugenol with fluconazole against clinical Candida isolates. J. Med. Microbiol. 59, 1178–1184. doi: 10.1099/jmm.0.020693-0
Ahmad, A., Khan, A., Manzoor, N., and Khan, L. A. (2010b). Evolution of ergosterol biosynthesis inhibitors as fungicidal against Candida. Microb. Pathog. 48, 35–41. doi: 10.1016/j.micpath.2009.10.001
Ahmad, A., Khan, A., and Manzoor, N. (2013). Reversal of efflux mediated antifungal resistance underlies synergistic activity of two monoterpenes with fluconazole. Eur. J. Pharm. Sci. 48, 80–86. doi: 10.1016/j.ejps.2012.09.016
Alves, C. T., Ferreira, I. C., Barros, L., Silva, S., Azeredo, J., and Henriques, M. (2014). Antifungal activity of phenolic compounds identified in flowers from North Eastern Portugal against Candida species. Future Microbiol. 9, 139–146. doi: 10.2217/fmb.13.147
Andrews, F. A., Beggs, W. H., and Sarosi, G. A. (1977). Influence of antioxidants on the bioactivity of amphotericin B. Antimicrob. Agents Chemother. 11, 615–618. doi: 10.1128/AAC.11.4.615
Bates, D. W., Su, L., Yu, D. T., Chertow, G. M., Seger, D. L., Gomes, D. R., et al. (2001). Correlates of acute renal failure in patients receiving parenteral amphotericin B. Kidney Int. 60, 1452–1459. doi: 10.1046/j.1523-1755.2001.00948.x
Beggs, W. H., Andrews, F. A., and Sarosi, G. A. (1978). Synergistic action of amphotericin B and antioxidants against certain opportunistic yeast pathogens. Antimicrob. Agents Chemother. 13, 266–270. doi: 10.1128/AAC.13.2.266
Ben-Ami, R., Garcia-Effron, G., Lewis, R. E., Gamarra, S., Leventakos, K., Perlin, D. S., et al. (2011). Fitness and virulence costs of Candida albicans FKS1 hot spot mutations associated with echinocandin resistance. J. Infect. Dis. 204, 626–635. doi: 10.1093/infdis/jir351
Berdal, J. E., Haagensen, R., Ranheim, T., and Bjornholt, J. V. (2014). Nosocomial candidemia; risk factors and prognosis revisited; 11 years experience from a Norwegian secondary hospital. PLoS ONE 9:e103916. doi: 10.1371/journal.pone.0103916
Borges, A., Ferreira, C., Saavedra, M. J., and Simoes, M. (2013). Antibacterial activity and mode of action of ferulic and gallic acids against pathogenic bacteria. Microb. Drug Resist. 19, 256–265. doi: 10.1089/mdr.2012.0244
Braga, P. C., Alfieri, M., Culici, M., and Dal Sasso, M. (2007). Inhibitory activity of thymol against the formation and viability of Candida albicans hyphae. Mycoses 50, 502–506. doi: 10.1111/j.1439-0507.2007.01412.x
Cao, Y., Huang, S., Dai, B., Zhu, Z., Lu, H., Dong, L., et al. (2009). Candida albicans cells lacking CaMCA1-encoded metacaspase show resistance to oxidative stress-induced death and change in energy metabolism. Fungal Genet. Biol. 46, 183–189. doi: 10.1016/j.fgb.2008.11.001
Chandra, J., Zhou, G., and Ghannoum, M. A. (2005). Fungal biofilms and antimycotics. Curr. Drug Targets 6, 887–894. doi: 10.2174/138945005774912762
Chandrasekar, P. (2011). Management of invasive fungal infections: a role for polyenes. J. Antimicrob. Chemother. 66, 457–465. doi: 10.1093/jac/dkq479
Chapman, S. W., Sullivan, D. C., and Cleary, J. D. (2008). In search of the holy grail of antifungal therapy. Trans. Am. Clin. Climatol. Assoc. 119, 197–215; discussion 215–196.
Cheah, H. L., Lim, V., and Sandai, D. (2014). Inhibitors of the glyoxylate cycle enzyme ICL1 in Candida albicans for potential use as antifungal agents. PLoS ONE 9:e95951. doi: 10.1371/journal.pone.0095951
Chirinos, R., Betalleluz-Pallardel, I., Huamán, A., Arbizu, C., Pedreschi, R., and Campos, D. (2009). HPLC-DAD characterisation of phenolic compounds from Andean oca (Oxalis tuberosa Mol.) tubers and their contribution to the antioxidant capacity. Food Chem. 113, 1243–1251. doi: 10.1016/j.foodchem.2008.08.015
Clancy, C. J., and Nguyen, M. H. (2011). At what cost echinocandin resistance? J. Infect. Dis. 204, 499–501. doi: 10.1093/infdis/jir355
Conti, B. J., Bufalo, M. C., Golim Mde, A., Bankova, V., and Sforcin, J. M. (2013). Cinnamic Acid is partially involved in propolis immunomodulatory action on human monocytes. Evid. Based Complement. Alternat. Med. 2013, 109864. doi: 10.1155/2013/109864
Cuellar-Cruz, M., Vega-Gonzalez, A., Mendoza-Novelo, B., Lopez-Romero, E., Ruiz-Baca, E., Quintanar-Escorza, M. A., et al. (2012). The effect of biomaterials and antifungals on biofilm formation by Candida species: a review. Eur. J. Clin. Microbiol. Infect. Dis. 31, 2513–2527. doi: 10.1007/s10096-012-1634-6
Cueva, C., Moreno-Arribas, M. V., Martin-Alvarez, P. J., Bills, G., Vicente, M. F., Basilio, A., et al. (2010). Antimicrobial activity of phenolic acids against commensal, probiotic and pathogenic bacteria. Res. Microbiol. 161, 372–382. doi: 10.1016/j.resmic.2010.04.006
da Silva, C. R., De Andrade Neto, J. B., De Sousa Campos, R., Figueiredo, N. S., Sampaio, L. S., Magalhaes, H. I., et al. (2014). Synergistic effect of the flavonoid catechin, quercetin, or epigallocatechin gallate with fluconazole induces apoptosis in Candida tropicalis resistant to fluconazole. Antimicrob. Agents Chemother. 58, 1468–1478. doi: 10.1128/aac.00651-13
D’Auria, F. D., Tecca, M., Strippoli, R., and Simonetti, N. (2001). In vitro activity of propyl gallate-azole drug combination against fluconazole- and itraconazole-resistant Candida albicans strains. Lett. Appl. Microbiol. 32, 220–223. doi: 10.1046/j.1472-765X.2001.00893.x
De Vita, D., Friggeri, L., D’auria, F. D., Pandolfi, F., Piccoli, F., Panella, S., et al. (2014). Activity of caffeic acid derivatives against Candida albicans biofilm. Bioorg. Med. Chem. Lett. 24, 1502–1505. doi: 10.1016/j.bmcl.2014.02.005
Drgona, L., Khachatryan, A., Stephens, J., Charbonneau, C., Kantecki, M., Haider, S., et al. (2014). Clinical and economic burden of invasive fungal diseases in Europe: focus on pre-emptive and empirical treatment of Aspergillus and Candida species. Eur. J. Clin. Microbiol. Infect. Dis. 33, 7–21. doi: 10.1007/s10096-013-1944-3
Endo, E. H., Cortez, D. A., Ueda-Nakamura, T., Nakamura, C. V., and Dias Filho, B. P. (2010). Potent antifungal activity of extracts and pure compound isolated from pomegranate peels and synergism with fluconazole against Candida albicans. Res. Microbiol. 161, 534–540. doi: 10.1016/j.resmic.2010.05.002
Evensen, N. A., and Braun, P. C. (2009). The effects of tea polyphenols on Candida albicans: inhibition of biofilm formation and proteasome inactivation. Can. J. Microbiol. 55, 1033–1039. doi: 10.1139/w09-058
Falagas, M. E., Apostolou, K. E., and Pappas, V. D. (2006). Attributable mortality of candidemia: a systematic review of matched cohort and case-control studies. Eur. J. Clin. Microbiol. Infect. Dis. 25, 419–425. doi: 10.1007/s10096-006-0159-2
Faria, N. C., Kim, J. H., Goncalves, L. A., Martins Mde, L., Chan, K. L., and Campbell, B. C. (2011). Enhanced activity of antifungal drugs using natural phenolics against yeast strains of Candida and Cryptococcus. Lett. Appl. Microbiol. 52, 506–513. doi: 10.1111/j.1472-765X.2011.03032.x
Feldman, M., Tanabe, S., Howell, A., and Grenier, D. (2012). Cranberry proanthocyanidins inhibit the adherence properties of Candida albicans and cytokine secretion by oral epithelial cells. BMC Complement. Altern. Med. 12:6. doi: 10.1186/1472-6882-12-6
Fogliani, B., Raharivelomanana, P., Bianchini, J. P., Bouraima-Madjebi, S., and Hnawia, E. (2005). Bioactive ellagitannins from Cunonia macrophylla, an endemic Cunoniaceae from New Caledonia. Phytochemistry 66, 241–247. doi: 10.1016/j.phytochem.2004.11.016
Fu, Z., Lu, H., Zhu, Z., Yan, L., Jiang, Y., and Cao, Y. (2011). Combination of baicalein and Amphotericin B accelerates Candida albicans apoptosis. Biol. Pharm. Bull. 34, 214–218. doi: 10.1248/bpb.34.214
Galati, G., Lin, A., Sultan, A. M., and O’brien, P. J. (2006). Cellular and in vivo hepatotoxicity caused by green tea phenolic acids and catechins. Free Radic. Biol. Med. 40, 570–580. doi: 10.1016/j.freeradbiomed.2005.09.014
Gehrke, I. T., Neto, A. T., Pedroso, M., Mostardeiro, C. P., Da Cruz, I. B., Silva, U. F., et al. (2013). Antimicrobial activity of Schinus lentiscifolius (Anacardiaceae). J. Ethnopharmacol. 148, 486–491. doi: 10.1016/j.jep.2013.04.043
Govindarajan, R., Vijayakumar, M., Singh, M., Rao Ch, V., Shirwaikar, A., Rawat, A. K., et al. (2006). Antiulcer and antimicrobial activity of Anogeissus latifolia. J. Ethnopharmacol. 106, 57–61. doi: 10.1016/j.jep.2005.12.002
Guo, N., Liu, J., Wu, X., Bi, X., Meng, R., Wang, X., et al. (2009). Antifungal activity of thymol against clinical isolates of fluconazole-sensitive and -resistant Candida albicans. J. Med. Microbiol. 58, 1074–1079. doi: 10.1099/jmm.0.008052-0
Hakki, M., Staab, J. F., and Marr, K. A. (2006). Emergence of a Candida krusei isolate with reduced susceptibility to caspofungin during therapy. Antimicrob. Agents Chemother. 50, 2522–2524. doi: 10.1128/aac.00148-06
Han, Y. (2007). Synergic anticandidal effect of epigallocatechin-O-gallate combined with amphotericin B in a murine model of disseminated candidiasis and its anticandidal mechanism. Biol. Pharm. Bull. 30, 1693–1696. doi: 10.1248/bpb.30.1693
Hirasawa, M., and Takada, K. (2004). Multiple effects of green tea catechin on the antifungal activity of antimycotics against Candida albicans. J. Antimicrob. Chemother. 53, 225–229. doi: 10.1093/jac/dkh046
Hirose, M., Takesada, Y., Tanaka, H., Tamano, S., Kato, T., and Shirai, T. (1998). Carcinogenicity of antioxidants BHA, caffeic acid, sesamol, 4-methoxyphenol and catechol at low doses, either alone or in combination, and modulation of their effects in a rat medium-term multi-organ carcinogenesis model. Carcinogenesis 19, 207–212. doi: 10.1093/carcin/19.1.207
Hossain, M. Z., Patel, K., and Kern, S. E. (2014). Salivary alpha-amylase, serum albumin, and myoglobin protect against DNA-damaging activities of ingested dietary agents in vitro. Food Chem. Toxicol. 70, 114–119. doi: 10.1016/j.fct.2014.05.002
Huang, S., Cao, Y. Y., Dai, B. D., Sun, X. R., Zhu, Z. Y., Cao, Y. B., et al. (2008). In vitro synergism of fluconazole and baicalein against clinical isolates of Candida albicans resistant to fluconazole. Biol. Pharm. Bull. 31, 2234–2236. doi: 10.1248/bpb.31.2234
Huffnagle, G. B., and Noverr, M. C. (2013). The emerging world of the fungal microbiome. Trends Microbiol. 21, 334–341. doi: 10.1016/j.tim.2013.04.002
Jin, J., Guo, N., Zhang, J., Ding, Y., Tang, X., Liang, J., et al. (2010). The synergy of honokiol and fluconazole against clinical isolates of azole-resistant Candida albicans. Lett. Appl. Microbiol. 51, 351–357. doi: 10.1111/j.1472-765X.2010.02900.x
Joly, V., Bolard, J., and Yeni, P. (1992). In vitro models for studying toxicity of antifungal agents. Antimicrob. Agents Chemother. 36, 1799–1804. doi: 10.1128/AAC.36.9.1799
Kalinowska, M., Piekut, J., Bruss, A., Follet, C., Sienkiewicz-Gromiuk, J., Swislocka, R., et al. (2014). Spectroscopic (FT-IR, FT-Raman, 1H, 13C NMR, UV/VIS), thermogravimetric and antimicrobial studies of Ca(II), Mn(II), Cu(II), Zn(II) and Cd(II) complexes of ferulic acid. Spectrochim. Acta A Mol. Biomol. Spectrosc. 122, 631–638. doi: 10.1016/j.saa.2013.11.089
Kanafani, Z. A., and Perfect, J. R. (2008). Antimicrobial resistance: resistance to antifungal agents: mechanisms and clinical impact. Clin. Infect. Dis. 46, 120–128. doi: 10.1086/524071
Kang, K., Fong, W. P., and Tsang, P. W. (2010). Antifungal activity of baicalein against Candida krusei does not involve apoptosis. Mycopathologia 170, 391–396. doi: 10.1007/s11046-010-9341-2
Kaufman, S. (1989). An evaluation of the possible neurotoxicity of metabolites of phenylalanine. J. Pediatr. 114, 895–900. doi: 10.1016/S0022-3476(89)80161-1
Kaufmann, W., Mellert, W., Van Ravenzwaay, B., Landsiedel, R., and Poole, A. (2005). Effects of styrene and its metabolites on different lung compartments of the mouse–cell proliferation and histomorphology. Regul. Toxicol. Pharmacol. 42, 24–36. doi: 10.1016/j.yrtph.2005.01.002
Khan, A., Ahmad, A., Khan, L. A., and Manzoor, N. (2014). Ocimum sanctum (L.) essential oil and its lead molecules induce apoptosis in Candida albicans. Res. Microbiol. 165, 411–419. doi: 10.1016/j.resmic.2014.05.031
Khan, M. S., and Ahmad, I. (2012). Antibiofilm activity of certain phytocompounds and their synergy with fluconazole against Candida albicans biofilms. J. Antimicrob. Chemother. 67, 618–621. doi: 10.1093/jac/dkr512
Khoddami, A., Wilkes, M. A., and Roberts, T. H. (2013). Techniques for analysis of plant phenolic compounds. Molecules 18, 2328–2375. doi: 10.3390/molecules18022328
Kleinegger, C. L., Lockhart, S. R., Vargas, K., and Soll, D. R. (1996). Frequency, intensity, species, and strains of oral Candida vary as a function of host age. J. Clin. Microbiol. 34, 2246–2254.
Kremer, D., Kosir, I. J., Kosalec, I., Koncic, M. Z., Potocnik, T., Cerenak, A., et al. (2013). Investigation of chemical compounds, antioxidant and antimicrobial properties of Teucrium arduini L. (lamiaceae). Curr. Drug Targets 14, 1006–1014. doi: 10.2174/1389450111314090009
Ksouri, R., Falleh, H., Megdiche, W., Trabelsi, N., Mhamdi, B., Chaieb, K., et al. (2009). Antioxidant and antimicrobial activities of the edible medicinal halophyte Tamarix gallica L. and related polyphenolic constituents. Food Chem. Toxicol. 47, 2083–2091. doi: 10.1016/j.fct.2009.05.040
Kuete, V., Nana, F., Ngameni, B., Mbaveng, A. T., Keumedjio, F., and Ngadjui, B. T. (2009). Antimicrobial activity of the crude extract, fractions and compounds from stem bark of Ficus ovata (Moraceae). J. Ethnopharmacol. 124, 556–561. doi: 10.1016/j.jep.2009.05.003
Kullberg, B. J., and Arendrup, M. C. (2015). Invasive candidiasis. N. Engl. J. Med. 373, 1445–1456. doi: 10.1056/NEJMra1315399
Lee, W., and Lee, D. G. (2014). An antifungal mechanism of curcumin lies in membrane-targeted action within Candida albicans. IUBMB Life 66, 780–785. doi: 10.1002/iub.1326
Lewis, J. S. II, and Graybill, J. R. (2008). Fungicidal versus fungistatic: what’s in a word? Expert Opin. Pharmacother. 9, 927–935. doi: 10.1517/14656566.9.6.927
Liu, M., Katerere, D. R., Gray, A. I., and Seidel, V. (2009). Phytochemical and antifungal studies on Terminalia mollis and Terminalia brachystemma. Fitoterapia 80, 369–373. doi: 10.1016/j.fitote.2009.05.006
Liu, W., Li, L. P., Zhang, J. D., Li, Q., Shen, H., Chen, S. M., et al. (2014). Synergistic antifungal effect of glabridin and fluconazole. PLoS ONE 9:e103442. doi: 10.1371/journal.pone.0103442
Ma, C. M., Abe, T., Komiyama, T., Wang, W., Hattori, M., and Daneshtalab, M. (2010). Synthesis, anti-fungal and 1,3-beta-D-glucan synthase inhibitory activities of caffeic and quinic acid derivatives. Bioorg. Med. Chem. 18, 7009–7014. doi: 10.1016/j.bmc.2010.08.022
Mahata, D., Mandal, S. M., Bharti, R., Gupta, V. K., Mandal, M., Nag, A., et al. (2014). Self-assembled cardanol azo derivatives as antifungal agent with chitin-binding ability. Int. J. Biol. Macromol. 69, 5–11. doi: 10.1016/j.ijbiomac.2014.05.017
Maistro, E. L., Angeli, J. P., Andrade, S. F., and Mantovani, M. S. (2011). In vitro genotoxicity assessment of caffeic, cinnamic and ferulic acids. Genet. Mol. Res. 10, 1130–1140. doi: 10.4238/vol10-2gmr1278
Manayi, A., Saeidnia, S., Faramarzi, M. A., Samadi, N., Jafari, S., Vazirian, M., et al. (2013). A comparative study of anti-Candida activity and phenolic contents of the calluses from Lythrum salicaria L. in different treatments. Appl. Biochem. Biotechnol. 170, 176–184. doi: 10.1007/s12010-013-0185-3
Maskovic, P., Solujic, S., Mihailovic, V., Mladenovic, M., Cvijovic, M., Mladenovic, J., et al. (2011). Phenolic compounds and biological activity of Kitaibelia vitifolia. J. Med. Food 14, 1617–1623. doi: 10.1089/jmf.2011.0013
Mendonca Ade, L., Da Silva, C. E., De Mesquita, F. L., Campos Rda, S., Do Nascimento, R. R., Ximenes, E. C., et al. (2009). Antimicrobial activities of components of the glandular secretions of leaf cutting ants of the genus Atta. Antonie Van Leeuwenhoek 95, 295–303. doi: 10.1007/s10482-009-9312-0
Messier, C., Epifano, F., Genovese, S., and Grenier, D. (2011). Inhibition of Candida albicans biofilm formation and yeast-hyphal transition by 4-hydroxycordoin. Phytomedicine 18, 380–383. doi: 10.1016/j.phymed.2011.01.013
Messier, C., and Grenier, D. (2011). Effect of licorice compounds licochalcone A, glabridin and glycyrrhizic acid on growth and virulence properties of Candida albicans. Mycoses 54, e801–e806. doi: 10.1111/j.1439-0507.2011.02028.x
Middelhoven, W. J. (1993). Catabolism of benzene compounds by ascomycetous and basidiomycetous yeasts and yeastlike fungi. A literature review and an experimental approach. Antonie Van Leeuwenhoek 63, 125–144. doi: 10.1007/BF00872388
Middelhoven, W. J., Coenen, A., Kraakman, B., and Sollewijn Gelpke, M. D. (1992). Degradation of some phenols and hydroxybenzoates by the imperfect ascomycetous yeasts Candida parapsilosis and Arxula adeninivorans: evidence for an operative gentisate pathway. Antonie Van Leeuwenhoek 62, 181–187. doi: 10.1007/BF00582578
Morales, G., Paredes, A., Sierra, P., and Loyola, L. A. (2008). Antimicrobial activity of three baccharis species used in the traditional medicine of Northern Chile. Molecules 13, 790–794. doi: 10.3390/molecules13040790
Morgan, J. (2005). Global trends in candidemia: review of reports from 1995-2005. Curr. Infect. Dis. Rep. 7, 429–439. doi: 10.1007/s11908-005-0044-7
Nakamura, Y., Torikai, K., and Ohigashi, H. (2001). Toxic dose of a simple phenolic antioxidant, protocatechuic acid, attenuates the glutathione level in ICR mouse liver and kidney. J. Agric. Food Chem. 49, 5674–5678. doi: 10.1021/jf0106594
Navarro-Martinez, M. D., Garcia-Canovas, F., and Rodriguez-Lopez, J. N. (2006). Tea polyphenol epigallocatechin-3-gallate inhibits ergosterol synthesis by disturbing folic acid metabolism in Candida albicans. J. Antimicrob. Chemother. 57, 1083–1092. doi: 10.1093/jac/dkl124
Nazaruk, J., Czechowska, S. K., Markiewicz, R., and Borawska, M. H. (2008). Polyphenolic compounds and in vitro antimicrobial and antioxidant activity of aqueous extracts from leaves of some Cirsium species. Nat. Prod. Res. 22, 1583–1588. doi: 10.1080/14786410701825053
Negri, M., Salci, T. P., Shinobu-Mesquita, C. S., Capoci, I. R., Svidzinski, T. I., and Kioshima, E. S. (2014). Early state research on antifungal natural products. Molecules 19, 2925–2956. doi: 10.3390/molecules19032925
Netea, M. G., Brown, G. D., Kullberg, B. J., and Gow, N. A. (2008). An integrated model of the recognition of Candida albicans by the innate immune system. Nat. Rev. Microbiol. 6, 67–78. doi: 10.1038/nrmicro1815
Nett, J., and Andes, D. (2006). Candida albicans biofilm development, modeling a host-pathogen interaction. Curr. Opin. Microbiol. 9, 340–345. doi: 10.1016/j.mib.2006.06.007
Newman, D. J., and Cragg, G. M. (2012). Natural products as sources of new drugs over the 30 years from 1981 to 2010. J. Nat. Prod. 75, 311–335. doi: 10.1021/np200906s
Niho, N., Shibutani, M., Tamura, T., Toyoda, K., Uneyama, C., Takahashi, N., et al. (2001). Subchronic toxicity study of gallic acid by oral administration in F344 rats. Food Chem. Toxicol. 39, 1063–1070. doi: 10.1016/S0278-6915(01)00054-0
Niimi, M., Firth, N. A., and Cannon, R. D. (2010). Antifungal drug resistance of oral fungi. Odontology 98, 15–25. doi: 10.1007/s10266-009-0118-3
Nohynek, L. J., Alakomi, H. L., Kahkonen, M. P., Heinonen, M., Helander, I. M., Oksman-Caldentey, K. M., et al. (2006). Berry phenolics: antimicrobial properties and mechanisms of action against severe human pathogens. Nutr. Cancer 54, 18–32. doi: 10.1207/s15327914nc5401_4
Nostro, A., Filocamo, A., Giovannini, A., Catania, S., Costa, C., Marino, A., et al. (2012). Antimicrobial activity and phenolic content of natural site and micropropagated Limonium avei (De Not.) Brullo & Erben plant extracts. Nat. Prod. Res. 26, 2132–2136. doi: 10.1080/14786419.2011.628669
Nowak, R., Olech, M., Pecio, L., Oleszek, W., Los, R., Malm, A., et al. (2014). Cytotoxic, antioxidant, antimicrobial properties and chemical composition of rose petals. J. Sci. Food Agric. 94, 560–567. doi: 10.1002/jsfa.6294
Odds, F. C., Brown, A. J., and Gow, N. A. (2003). Antifungal agents: mechanisms of action. Trends Microbiol. 11, 272–279. doi: 10.1016/S0966-842X(03)00117-3
Ozcelik, B., Kartal, M., and Orhan, I. (2011). Cytotoxicity, antiviral and antimicrobial activities of alkaloids, flavonoids, and phenolic acids. Pharm. Biol. 49, 396–402. doi: 10.3109/13880209.2010.519390
Pereira, A. P., Ferreira, I. C., Marcelino, F., Valentao, P., Andrade, P. B., Seabra, R., et al. (2007). Phenolic compounds and antimicrobial activity of olive (Olea europaea L. Cv. Cobrancosa) leaves. Molecules 12, 1153–1162. doi: 10.3390/12051153
Pereira, D., Valentão, P., Pereira, J., and Andrade, P. (2009). Phenolics: from chemistry to biology. Molecules 14, 2202–2211. doi: 10.3390/molecules14062202
Pfaller, M. A., Castanheira, M., Messer, S. A., Moet, G. J., and Jones, R. N. (2010). Variation in Candida spp. distribution and antifungal resistance rates among bloodstream infection isolates by patient age: report from the SENTRY Antimicrobial Surveillance Program (2008-2009). Diagn. Microbiol. Infect. Dis. 68, 278–283. doi: 10.1016/j.diagmicrobio.2010.06.015
Pfaller, M. A., Moet, G. J., Messer, S. A., Jones, R. N., and Castanheira, M. (2011). Candida bloodstream infections: comparison of species distributions and antifungal resistance patterns in community-onset and nosocomial isolates in the SENTRY Antimicrobial Surveillance Program, 2008-2009. Antimicrob. Agents Chemother. 55, 561–566. doi: 10.1128/aac.01079-10
Pinto, E., Vale-Silva, L., Cavaleiro, C., and Salgueiro, L. (2009). Antifungal activity of the clove essential oil from Syzygium aromaticum on Candida, Aspergillus and dermatophyte species. J. Med. Microbiol. 58, 1454–1462. doi: 10.1099/jmm.0.010538-0
Polke, M., Hube, B., and Jacobsen, I. D. (2015). Candida survival strategies. Adv. Appl. Microbiol. 91, 139–235. doi: 10.1016/bs.aambs.2014.12.002
Praphanphoj, V., Boyadjiev, S. A., Waber, L. J., Brusilow, S. W., and Geraghty, M. T. (2000). Three cases of intravenous sodium benzoate and sodium phenylacetate toxicity occurring in the treatment of acute hyperammonaemia. J. Inherit. Metab. Dis. 23, 129–136. doi: 10.1023/A:1005661631281
Pretto, J. B., Cechinel-Filho, V., Noldin, V. F., Sartori, M. R., Isaias, D. E., and Cruz, A. B. (2004). Antimicrobial activity of fractions and compounds from Calophyllum brasiliense (Clusiaceae/Guttiferae). Z. Naturforsch. C 59, 657–662. doi: 10.1515/znc-2004-9-1009
Rane, H. S., Bernardo, S. M., Howell, A. B., and Lee, S. A. (2014). Cranberry-derived proanthocyanidins prevent formation of Candida albicans biofilms in artificial urine through biofilm– and adherence-specific mechanisms. J. Antimicrob. Chemother. 69, 428–436. doi: 10.1093/jac/dkt398
Rangkadilok, N., Tongchusak, S., Boonhok, R., Chaiyaroj, S. C., Junyaprasert, V. B., Buajeeb, W., et al. (2012). In vitro antifungal activities of longan (Dimocarpus longan Lour.) seed extract. Fitoterapia 83, 545–553. doi: 10.1016/j.fitote.2011.12.023
Rauha, J. P., Remes, S., Heinonen, M., Hopia, A., Kahkonen, M., Kujala, T., et al. (2000). Antimicrobial effects of Finnish plant extracts containing flavonoids and other phenolic compounds. Int. J. Food Microbiol. 56, 3–12. doi: 10.1016/S0168-1605(00)00218-X
Rautemaa, R., and Ramage, G. (2011). Oral candidosis–clinical challenges of a biofilm disease. Crit. Rev. Microbiol. 37, 328–336. doi: 10.3109/1040841x.2011.585606
Salvador, M. J., Zucchi, O. L. A. D., Candido, R. C., Ito, I. Y., and Dias, D. A. (2004). in vitro antimicrobial activity of crude extracts and isolated constituents of Alternanthera maritima. Pharm. Biol. 42, 138–148. doi: 10.1080/13880200490511954
Sanglard, D., Coste, A., and Ferrari, S. (2009). Antifungal drug resistance mechanisms in fungal pathogens from the perspective of transcriptional gene regulation. FEMS Yeast Res. 9, 1029–1050. doi: 10.1111/j.1567-1364.2009.00578.x
Seneviratne, C. J., Wong, S. S., Yuen, K. Y., Meurman, J. H., Parnanen, P., Vaara, M., et al. (2011). Antifungal susceptibility and virulence attributes of bloodstream isolates of Candida from Hong Kong and Finland. Mycopathologia 172, 389–395. doi: 10.1007/s11046-011-9444-4
Shahzad, M., Sherry, L., Rajendran, R., Edwards, C. A., Combet, E., and Ramage, G. (2014). Utilising polyphenols for the clinical management of Candida albicans biofilms. Int. J. Antimicrob. Agents 44, 269–273. doi: 10.1016/j.ijantimicag.2014.05.017
Sharma, M., Manoharlal, R., Puri, N., and Prasad, R. (2010). Antifungal curcumin induces reactive oxygen species and triggers an early apoptosis but prevents hyphae development by targeting the global repressor TUP1 in Candida albicans. Biosci. Rep. 30, 391–404. doi: 10.1042/bsr20090151
Sieniawska, E., Baj, T., Los, R., Skalicka-Wozniak, K., Malm, A., and Glowniak, K. (2013). Phenolic acids content, antioxidant and antimicrobial activity of Ligusticum mutellina L. Nat. Prod. Res. 27, 1108–1110. doi: 10.1080/14786419.2012.698413
Siikala, E., Rautemaa, R., Richardson, M., Saxen, H., Bowyer, P., and Sanglard, D. (2010). Persistent Candida albicans colonization and molecular mechanisms of azole resistance in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) patients. J. Antimicrob. Chemother. 65, 2505–2513. doi: 10.1093/jac/dkq354
Simonetti, G., Simonetti, N., and Villa, A. (2003). Increase of activity of tioconazole against resistant microorganisms by the addition of butylated hydroxyanisole. Int. J. Antimicrob. Agents 22, 439–443. doi: 10.1016/S0924-8579(03)00120-1
Simonetti, G., Villa, A., and Simonetti, N. (2002). Enhanced contact activity of fluconazole in association with antioxidants against fluconazole-resistant organisms. J. Antimicrob. Chemother. 50, 257–259. doi: 10.1093/jac/dkf102
Strippoli, V., Dauria, F. D., Tecca, M., Callari, A., and Simonetti, G. (2000). Propyl gallate increases in vitro antifungal imidazole activity against Candida albicans. Int. J. Antimicrob. Agents 16, 73–76. doi: 10.1016/S0924-8579(00)00200-4
Sung, W. S., and Lee, D. G. (2010). Antifungal action of chlorogenic acid against pathogenic fungi, mediated by membrane disruption. Pure Appl. Chem. 82, 219–226. doi: 10.1351/PAC-CON-09-01-08
Teodoro, G. R., Brighenti, F. L., Delbem, A. C., Delbem, A. C., Khouri, S., Gontijo, A. V., et al. (2015). Antifungal activity of extracts and isolated compounds from Buchenavia tomentosa on Candida albicans and non-albicans. Future Microbiol. 10, 917–927. doi: 10.2217/fmb.15.20
Vanden Bossche, H., Ausma, J., Bohets, H., Vermuyten, K., Willemsens, G., Marichal, P., et al. (2004). The novel azole R126638 is a selective inhibitor of ergosterol synthesis in Candida albicans, Trichophyton spp., and Microsporum canis. Antimicrob. Agents Chemother. 48, 3272–3278. doi: 10.1128/aac.48.9.3272-3278.2004
Vuong, C., Kocianova, S., Voyich, J. M., Yao, Y., Fischer, E. R., Deleo, F. R., et al. (2004). A crucial role for exopolysaccharide modification in bacterial biofilm formation, immune evasion, and virulence. J. Biol. Chem. 279, 54881–54886. doi: 10.1074/jbc.M411374200
Wang, C., Cheng, H., Guan, Y., Wang, Y., and Yun, Y. (2009). [In vitro activity of gallic acid against Candida albicans biofilms]. Zhongguo Zhong Yao Za Zhi 34, 1137–1140.
Wang, S. S., Wang, D. M., Pu, W. J., and Li, D. W. (2013). Phytochemical profiles, antioxidant and antimicrobial activities of three Potentilla species. BMC Complement. Altern. Med. 13:321. doi: 10.1186/1472-6882-13-321
Williams, D. W., Kuriyama, T., Silva, S., Malic, S., and Lewis, M. A. (2011). Candida biofilms and oral candidosis: treatment and prevention. Periodontol. 2000 55, 250–265. doi: 10.1111/j.1600-0757.2009.00338.x
Wingard, J. R., Kubilis, P., Lee, L., Yee, G., White, M., Walshe, L., et al. (1999). Clinical significance of nephrotoxicity in patients treated with amphotericin B for suspected or proven aspergillosis. Clin. Infect. Dis. 29, 1402–1407. doi: 10.1086/313498
Wong, S. S., Samaranayake, L. P., and Seneviratne, C. J. (2014). In pursuit of the ideal antifungal agent for Candida infections: high-throughput screening of small molecules. Drug Discov. Today 19, 1721–1730. doi: 10.1016/j.drudis.2014.06.009
Yano, S., Yamaguchi, T., Kanazawa, I., Ogawa, N., Hayashi, K., Yamauchi, M., et al. (2007). The uraemic toxin phenylacetic acid inhibits osteoblastic proliferation and differentiation: an implication for the pathogenesis of low turnover bone in chronic renal failure. Nephrol. Dial. Transplant. 22, 3160–3165. doi: 10.1093/ndt/gfm455
Yun, J., Lee, H., Ko, H. J., Woo, E. R., and Lee, D. G. (2015). Fungicidal effect of isoquercitrin via inducing membrane disturbance. Biochim. Biophys. Acta 1848, 695–701. doi: 10.1016/j.bbamem.2014.11.019
Zengin, N., Yuzbasioglu, D., Unal, F., Yilmaz, S., and Aksoy, H. (2011). The evaluation of the genotoxicity of two food preservatives: sodium benzoate and potassium benzoate. Food Chem. Toxicol. 49, 763–769. doi: 10.1016/j.fct.2010.11.040
Zhang, L., Chang, W., Sun, B., Groh, M., Speicher, A., and Lou, H. (2011). Bisbibenzyls, a new type of antifungal agent, inhibit morphogenesis switch and biofilm formation through upregulation of DPP3 in Candida albicans. PLoS ONE 6:e28953. doi: 10.1371/journal.pone.0028953
Keywords: Candida, phenolic acids, phenolic compounds, antifungal effect, synergism
Citation: Teodoro GR, Ellepola K, Seneviratne CJ and Koga-Ito CY (2015) Potential Use of Phenolic Acids as Anti-Candida Agents: A Review. Front. Microbiol. 6:1420.doi: 10.3389/fmicb.2015.01420
Received: 15 September 2015; Accepted: 30 November 2015;
Published: 21 December 2015.
Edited by:
Tzi Bun Ng, The Chinese University of Hong Kong, ChinaReviewed by:
Dominique Sanglard, University of Lausanne and University Hospital Center, SwitzerlandSiddharth Kaushal Tripathi, University of Mississippi, USA
Copyright © 2015 Teodoro, Ellepola, Seneviratne and Koga-Ito. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Cristiane Y. Koga-Ito, Y3Jpc3RpYW5lQGljdC51bmVzcC5icg==; Chaminda J. Seneviratne, amF5YUBudXMuZWR1LnNn; amF5YUBoa3UuaGs=